Oral leukoplakia is a common clinical finding with a high risk of malignant transformation. Topical application of chemopreventive agents provide an attractive strategy in an attempt to effectively control the lesions with less toxicity than that in systemic administration. Its efficacy, however, is controversial due to some inherent limitations. In this proposed study, it is assumed that topical application of 585 nm pulsed dye laser and mucosal-adherent film (MAF) will produce a significant improvement of current topical approach. The long-term objectives of the proposal are to develop a novel combination strategy for chemoprevention of oral leukoplakia. The specific aims are (1) optimizing laser parameters; (2) fabricating the topical film containing 13-cis-retinoid acid (13c-RA); and (3) determine if such a combination produce synergic effects so that clinical application would be of significant benefit. The optimal laser parameters will be determined through quantity of microvascular density with fluorescent imagining and immunostaining techniques, in hamster model. The potential side-effect in local mucosa and ideal dosage of the agent used in MAF will be evaluated in the hamster model. The efficacy of new strategy will be determined by compared it with routine systemic administration and topical solution painting, in cheek pouch of hamster model bearing pre-malignant lesions. To our knowledge this is the first attempt to combine laser microvascular targeting, polymer film, and chemopreventive techniques for cancer prevention. This proposed strategy, if successful, is very likely to provide an alternative with higher efficacy and less toxicity than current methods. It also has extensive applications in prevention of skin cancer or cancers in other accessible and superficial areas.